Hydrophosphonylation of aldehydes

The catal)rtic enantioselective h)rdrophosphonylation of aldehydes was first reported in 1993 by Shibuya and coworkers. These early results showed that the addition of diethylphosphite (6.105) to benzaldehyde (6.01) could be catalysed by the titanium complex formed from ligand (6.58) with moderate enantioselectivity in the a-hydroxyphosphonate product (6.106). The titanium catalyst serves to facilitate conversion of the phosphite into the tautomer HOP(OEt)2 and activates the aldehyde towards addition. 

LaLi3tris(binaphthoxide) catalysts (LLB catalyst, see Section 7.1) have also been used for this reaction,although the method of preparation of the catalyst is important for very high selectivities. The LLB catalyst (6.107) was prepared by mixing LaCl3.7H20 (1 equiv.) BINOL dilithium salt (2.7 equiv.) and sodium 

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Scheme 5-32 Titanium alkoxide-catalyzed asymmetric hydrophosphonylation of aldehydes...

Scheme 5-33 LLB-catalyzed asymmetric hydrophosphonylation of aldehydes and a proposed mechanism LLB = La/Li/BINOL...

In comparison to related P(III) chemistry, metal-catalyzed additions of P-H bonds in P(V) compounds to unsaturated substrates have been studied in more detail, and several synthetically useful processes have been developed. In particular, the use of heterobimetallic BINOL-based catalysts allows asymmetric hydrophosphonylation of aldehydes and imines in high yield and enantiomeric excess. 

Moreover, ALB was found to be also useful for the hydrophosphonylation of aldehydes. ALB and LLB can thus be used in a complementary manner for the hydrophosphonylation of aldehydes. 

A salalen ligand (a hybrid salicylideneimine-salicylamine) has been coordinated to aluminium to serve as an enantioselective catalyst for aldehyde hydrophosphonylation of aldehydes.278... 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

Catalytic Enantioselective Hydrophosphonylation of Aldehydes. LLB catalyzes the hydrophosphonylations of aldehydes with dimethyl phosphite to afford a-hydroxy phosphonates with high optical purity (eq 7). In some cases, the aldehyde needs to be added slowly to the mixture of LLB and phosphite in THF. For some aromatic aldehydes, another catalyst, Li[Al(binol)2] (ALB), gives better results. Imines also react with dimethyl phosphite in a highly enantioselective manner when potassium-based complexes (K3[Ln(binol)3], LnPB) are used as catalysts. ... 

Heterobimetallic catalysis mediated by LnMB complexes (Structures 2 and 22) represents the first highly efficient asymmetric catalytic approach to both a-hydro and c-amino phosphonates [112], The highly enantioselective hydrophosphonylation of aldehydes [170] and acyclic and cyclic imines [171] has been achieved. The proposed catalytic cycle for the hydrophosphonylation of acyclic imines is shown representatively in Scheme 10. Potassium dimethyl phosphite is initially generated by the deprotonation of dimethyl phosphite with LnPB and immediately coordinates to the rare earth metal center via the oxygen. This adduct then produces with the incoming imine an optically active potassium salt of the a-amino phosphonate, which leads via proton-exchange reaction to an a-amino phosphonate and LnPB. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

A logical extension of these themes is for one catalyst to activate both the P-nucleophile and the unsaturated electrophile. This approach has been especially popular in asymmetric hydrophosphonylation of aldehydes and imines, which has been reviewed recently [59]. 

The hydrophosphonylation of aldehydes can also proceed enantioselectively in the presence of chiral nonracemic Lewis acids and some bifunctional catalysts and a small subchapter discusses recent advances in this area. 

Some of the metal-based catalysts used in the asymmetric hydrophosphonylation of aldehydes (see Section 6.4) can also be applied to the phosphonylation of imines. For instance, Shibasaki s heterobimetallic BINOL complexes work well for the catalytic asymmetric hydrophosphonylation of imines. In this case lanthanum-potassium-BINOL complexes (6.138) have been found to provide the highest enantioselectivities for the hydrophosphonylation of acyclic imines (6.139). The hydrophosphonylation of cyclic imines using heterobimetallic lanthanoid complexes has been reported. Ytterbium and samarium complexes in combination with cyclic phosphites have shown the best results in the cases investigated so far. For example, 3-thiazoline (6.140) is converted into the phosphonate (6.141) with 99% ee using ytterbium complex (6.142) and dimethyl phosphite (6.108). The aluminium(salalen) complex (6.110) developed by Katsuki and coworkers also functions as an effective catalyst for the hydrophosphonylation of both aromatic and aliphatic aldimines providing the resulting a-aminophosphonate with 81-91% ee. ... 

The chiral catalyst (352) has been detected by low-temperature NMR and applied in a highly efficient and enantioselective hydrophosphonylation of aldehydes (Scheme 80). ... 

For pioneering work on the highly enantioselective one-pot reaction of in situ preformed imines using a chiral salalen-ahiminiim catalyst, see B. Saito, H. Egami, T. Katsuki, J. Am. Chem. Soc. 2007, 129, 1978-1986. Synthesis of an optically active Al(salalen) complex and its application to catalytic hydrophosphonylation of aldehydes and aldimines. 

HYDROPHOSPHONYLATION OF ALDEHYDES AND NONACTIVATED KETONES BY CHARGE-NEUTRAL HOMOLEPTIC AND HETEROLEPTIC COMPLEXES OF LARGE ALKALINE EARTHS... 

Ternary and quaternary a-hydroxy-phosphonates, an important class of biologically active compounds, are commonly obtained by addition of dialkylphosphites onto aldehydes or ketones [30]. Well-defined mono- or bimetallic complexes of rare-earth metals, titanium, or aluminum have emerged over the past two decades as effective catalysts for this so-called hydrophosphonylation of aldehydes [31] and, with more difficulty, that of ketones [31c,d, 32], which are far less reactive because of their lower electrophilicity. In some cases, good enantioselectivities could be achieved thanks to the use of chiral metal-based precatalysts [31, 32], Despite their several similarities with rare-earth elements, we were surprised to see that discrete complexes of the large Ae metals had never been utilized to catalyze hydrophosphonylation reactions. 

In fact, we found that hydrophosphonylation of aldehydes and nonactivated ketones could be achieved selectively and rapidly at room temperature using very low catalytic loadings (as low as 0.02 mol%) of the simple Ae[N(SiMe3)2l2(THF)2 complexes (Ae = Ca, Sr, Ba) (Scheme 28.11, Table 28.7) [33]. Indeed these homoleptic Ae precatalysts turned out as... 

Scheme 28.11 Ae heteroleptic and homoleptic complexes screened for the hydrophosphonylation of aldehydes and ketones [33].

The asymmetric hydrophosphonylation of aldehydes has been achieved using a catalyst based upon a triaminoiminophosphorane (Scheme 4.155) [245]. This was an interesting approach to this chemistry and generated the a-hydroxyphosphonates in excellent yields with high enantioselectivity. In addition to the hydrophosphonylation chemistry, the authors also investigated how readily common bases deprotonated phosphites in order to provide... 

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